Formulation, in vitro evaluation and therapeutic effect of chitosan coated pluronic F127 micelles containing miltefosine for the treatment of visceral leishmaniasis in domestic dogs naturally infected by Leishmania infantum

IF 2.2 3区农林科学 Q1 VETERINARY SCIENCES

Research in veterinary science Pub Date : 2024-11-20 DOI:10.1016/j.rvsc.2024.105467

Zahra Alizadeh , Mehdi Mohebali , Behzad Aghabarari , Zabihollah Zarei , Gholamreza Hassanpour , Seyed Ebrahim Eskandari , Mehdi Parsaei , Shahram Jamshidi , Abbas Rahimi Foroushani , Hossein Keshavarz , Behnaz Akhoundi , Zahra Heidari , Fatemeh Mohebali , Seyedeh Parastoo Yasini , Akram Hassanpour

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Abstract

There are a limited number of chemotherapeutic agents for the treatment canine visceral leishmaniasis (CVL). This study aimed to formulate and assess micellar formulation of miltefosine (MTF) to increase antileishmanial therapeutic effects in dogs naturally infected by Leishmania (L) infantum for the first time. MTF loaded pluronic F127 (PF/MTF) micelles were formulated and coated with chitosan (Cs/PF/MTF). Toxicity of compounds was evaluated. The in vitro and in vivo antileishmanial effect of Cs/PF/MTF was examined in L. infantum promastigotes and amastigotes as well as naturally infected dogs by L. infantum. In-vitro efficacy studies in promastigotes and amastigotes demonstrated that inhibitory concentration (IC50) of Cs/PF/MTF was significantly lower in comparison to miltefosine. In vivo data showed that Cs/PF/MTF is more effective against CVL compared with miltefosine alone. The result of this study indicated that intravenous injection of new formulation of Cs/PF/MTF was tolerated and treated on L. infantum naturally infected dogs with the dosages of 170 μg/kg daily for 28 days.

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含有米替福新的壳聚糖包覆pluronic F127胶束的配方、体外评价和治疗效果，用于治疗受婴儿利什曼原虫自然感染的家犬的内脏利什曼病

目前用于治疗犬内脏利什曼病（CVL）的化疗药物数量有限。本研究旨在首次配制和评估米替福新（MTF）胶束制剂，以提高犬自然感染婴儿利什曼病（L）的抗利什曼病治疗效果。制备了负载 MTF 的pluronic F127（PF/MTF）胶束，并用壳聚糖（Cs/PF/MTF）包被。对化合物的毒性进行了评估。Cs/PF/MTF 的体外和体内抗利什曼病效果在幼虫原虫和非原虫以及被幼虫自然感染的狗身上进行了检验。对原生体和母细胞的体外药效研究表明，Cs/PF/MTF 的抑制浓度（IC50）明显低于米替福新。体内数据显示，与单独使用米替福新相比，Cs/PF/MTF 对 CVL 更有效。该研究结果表明，静脉注射 Cs/PF/MTF 新制剂对自然感染幼犬的耐受性良好，每天 170 μg/kg 的剂量可连续治疗 28 天。

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来源期刊

Research in veterinary science 农林科学-兽医学

CiteScore

4.40

自引率

4.20%

发文量

312

审稿时长

75 days

期刊介绍： Research in Veterinary Science is an International multi-disciplinary journal publishing original articles, reviews and short communications of a high scientific and ethical standard in all aspects of veterinary and biomedical research. The primary aim of the journal is to inform veterinary and biomedical scientists of significant advances in veterinary and related research through prompt publication and dissemination. Secondly, the journal aims to provide a general multi-disciplinary forum for discussion and debate of news and issues concerning veterinary science. Thirdly, to promote the dissemination of knowledge to a broader range of professions, globally. High quality papers on all species of animals are considered, particularly those considered to be of high scientific importance and originality, and with interdisciplinary interest. The journal encourages papers providing results that have clear implications for understanding disease pathogenesis and for the development of control measures or treatments, as well as those dealing with a comparative biomedical approach, which represents a substantial improvement to animal and human health. Studies without a robust scientific hypothesis or that are preliminary, or of weak originality, as well as negative results, are not appropriate for the journal. Furthermore, observational approaches, case studies or field reports lacking an advancement in general knowledge do not fall within the scope of the journal.